The primary goal of this COBRE renewal will remain the development of a critical mass of independently funded investigators who study the genetic and immunologic mechanisms that promote chronic inflammation, to understand its role in disease and, ultimately, to improve patient outcome. The success of the first cycle of this COBRE is represented by the retention, as faculty members, of 8 of the 9 promising junior investigators (PJIs) who started the program. Seven of them are independently funded. Mentors and PJIs generated a combined 148 peer reviewed publications of which 41% were authored or co-authored by the PJIs. The newly selected 8 PJIs have the unique opportunity to study a large local population of minority individuals, who represent approximately 50% of the patients seen at LSU Health Sciences Center (LSUHSC). This population suffers disproportionately from cancer, chronic infections, cardiovascular disease and other diseases considered to have a chronic inflammatory component. As in the initial cycle, most of our new PJIs are minority faculty, who are generally underrepresented in the pool of federally funded researchers. To optimize their future development and their competitiveness we have leveraged the scientific and clinical expertise at the principal academic medical centers in south Louisiana; LSUHSC, Tulane Medical Center and Ochsner Clinic Foundation. The unifying hypothesis is that chronic inflammation is the result of a dysfunctional immune response to an offending agent, causing tissue damage instead of protecting the host. Understanding the mechanisms that subvert the immune response in disease can provide insight into novel prevention and therapeutic approaches to these conditions. This concept will be studied in 5 principal projects that will determine the molecular link between inflammation and cancer (Projects 1, 2 and 3) and will evaluate the role of inflammation in chronic infections (Project 4 and 5). A limited number of early stage projects will also be supported to ensure access to a pipeline of junior investigators. The PJIs are mentored by a team of experienced and well funded senior scientists, and supported by several scientific cores. In addition, a Faculty Development Core will ensure their career advancement. The PJIs will be members of the proposed Center for Research in Chronic Inflammation and Disease (CRICD).